Abuse of the psychostimulant 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") has increased dramatically, emphasizing the need for understanding its mechanisms of action in order to manage overdose, toxicity, and psychological and physiological responses associated with MDMA use. The acute affects of MDMA include feelings of mental stimulation, emotional warmth, closeness and empathy, decreased anxiety, and a general sense of well-being; however, chronic use of MDMA is associated with marked depression, sleep disorders, and increased anxiety, impulsiveness, and hostility. Although the serotonin (5-HT) neurotransmitter system is thought to play a role in the behavioral effects of MDMA, the exact 5-HT receptors involved in mediating these effects are not well established. Behavioral sensitization to acute MDMA-induced hyperactivity appears to be associated with a functional reduction in the sensitivity of 5-HT2CR during withdrawal. The purpose of the present series of experiments is to further analyze the contribution of the 5-HT2CR to the withdrawal state evoked by MDMA and to explore the location of the 5-HT2CR within the DA mesoaccumbens pathway, which is thought to be critically important in mediating the behavioral effects of psychostimulants.